Project description:Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a novel nucleoid-associated protein that specifically binds AT-rich regions of the genome, including regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM/PGL, and the PE/PPE families of antigenic proteins. Comparison of genome-wide binding data with expression data indicates that Lsr2 binding results in transcriptional repression. Domain swamping experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C-terminal DNA binding domain. NMR analysis of the DNA binding domain of Lsr2 and its interaction with DNA reveals a novel structure and a unique mechanism that enables Lsr2 to discriminately target AT-rich sequences through interactions with the minor groove of DNA. Taken together, we provide evidence that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve an equivalent function as the Enterobacteriaceae H-NS, coordinating global gene regulation and virulence in this group of medically important bacteria.

2009-11-15 | GSE18652 | GEO

RIP-seq identification of RNAs enriched on RNA polymerase and the primary sigma factor (sigma A) in Mycobacterium smegmatis

Project description:6S RNA is a small RNA with specific secondary structure that associates with the complex of RNA polymerase (RNAP) and the primary sigma factor in majority of bacteria. In mycobacteria, Ms1 interacts with the RNAP core without the sigma factor and probably replaces 6S RNA. To identify RNAs that have a similar function as Ms1 or to identify a new 6S RNA in mycobacteria, we sequenced RNAs that co-immunoprecipitated with RNAP or the primary sigma factor sigma A. We also sequenced total RNA isolated from the lysate (input sample). We expect that putative regulatory RNAs are enriched in RNA polymerase or sigma A samples compared to the inputs. The experiment was performed in exponential and stationary phase of growth.

2024-02-09 | E-MTAB-11692 | biostudies-arrayexpress

Dual RNA-sequencing of macrophages infected with Mycobacterium avium reveals host-pathogen interaction in the context of clarithromycin treatment

Project description:Background: Mycobacterium avium is an opportunistic pathogen that requires complex multidrug treatment. Macrolides, like clarithromycin, are the cornerstone of treatment, but even macrolide-based treatment regimens have suboptimal outcomes. Combining transcriptomic profiling of macrophages and mycobacteria in an in vitro infection model may increase our understanding of the host-pathogen interaction and the effect of antibiotic treatment. Methods: To investigate the molecular interplay between pathogen and host, we developed an optimized protocol for dual RNA-sequencing of human monocyte-derived macrophages infected with M. avium. Results: Upon phagocytosis, host defense processes including immune activation and pathogen recognition were upregulated, while M. avium upregulated expression of PE/PPE genes, which are important for immune recognition. Clarithromycin did not affect gene regulation of the host; the effect of clarithromycin on M. avium gene expression was very different in RPMI compared to intracellular mycobacteria, likely due to the influence of the host environment on expression of the important regulatory WhiB genes. Conclusions These data identify the distinct stress responses of M. avium upon infection and clarithromycin treatment and underline the importance of taking the intracellular localization and interaction with the host into account when studying antibiotics against intracellular pathogens.

2024-01-01 | GSE213117 | GEO

Recognition of host-protective immune activation by Mycobacterium tuberculosis

Project description:The cytokine interferon-γ is a principal effector of macrophage activation and immune resistance to mycobacterial infection; however, pathogenic mycobacteria are capable of surviving in interferon-γ-activated macrophages by largely unknown mechanisms. We found that interferon-γ specifically bound to pathogenic mycobacteria and enhanced their growth in culture. Proteomic and electron microscopy analyses revealed that interferon-γ directly triggers proliferative activity and virulence phenotype in pathogenic mycobacteria that allow them to survive and grow inside macrophages. These findings suggest that pathogenic mycobacteria may have evolved eukaryotic-like signal transduction mechanisms to recognize host-protective immune activation.

2024-09-05 | PXD038542 | Pride

Mycobacterium

Project description:Analysis of isoniazid reaction mechanismes in mycobacteria.

| PRJDB14475 | ENA

A novel copper-responsive regulon in Mycobacterium tuberculosis.

Project description:In this study, we report the identification of a five-locus copper-inducible regulon in Mycobacterium tuberculosis. The identification of a copper responsive regulon unique to pathogenic Mycobacteria suggests copper homeostasis must be maintained during an infection.

2010-10-27 | GSE23498 | GEO

Mycobacterium sp

Project description:Mycobacteria clinical isolation - Limpopo - South Africa

| PRJNA1215970 | ENA